The molecular basis of regulation of ribonucleotide reduction in E. coli lay in a number of association-dissociation reactions between the proteins, ribotide reductase proteins B1 and B2, and possibly thioredoxin and thioredoxin reductase. Understanding of this system of multiple equilibria is being approached through ultracentrifugational studies on the purified reductase proteins. A second approach towards elucidating the critical regulation role of ribotide reductase in vivo is an attempt to detect any high molecular weight species containing ribotide reductase in crude extracts prepared under conditions where the levels of ribotide reductase approach that required to support DNA synthesis in vivo.